Impact of T‐cell receptor Vβ haplotypes on the development of dermatitis in DS‐Nh mice: synergistic production of interleukin‐13 caused by staphylococcal enterotoxin C and peptide glycans from Staphylococcus aureus

Summary Although the pathogenic role of interleukin-13 (IL-13) is a key for atopic dermatitis (AD), the mechanism of IL-13 production in AD remains unclear. To investigate the role of the T-cell receptor Vβ (TCR Vβ) haplotype in the development of dermatitis and the production of IL-13 in the naturally occurring dermatitis model by staphylococcal enterotoxin C (SEC)-producing Staphylococcus aureus, we raised DS-Nh mice harbouring the TCR Vβa haplotype with a central deletion in the TCRBV gene segments, including TCR Vβ8S2. Observation and histopathological analysis of the two mouse substrains with spontaneous dermatitis indicated that later onset and weaker severity of AD-like dermatitis were identified in mice with TCR Vβa compared to those with TCR Vβb. Immunohistochemical examination revealed the infiltration of a large number of CD4-bearing T cells in the skin lesions in mice with TCR Vβb but not in those with TCR Vβa. Interestingly, much lower levels of serum IL-13 were detected in mice with the TCR Vβa than in those with the TCR Vβb haplotype. In vitro, synthetic ligands (Pam2CSK4) of toll-like receptor 2 (TLR2) synergistically produced IL-13 with SEC in splenocytes of mice with TCR Vβb but not of those with TCR Vβa, and natural killer T cells were essential for this synergism. Our findings suggested that this TCR Vβ-haplotype-dependent synergism with TLR2 plays an important role in the development of AD-like dermatitis in DS-Nh mice.